ABSTRACT: PROJECT 2. Clinical and molecular determinants of HIV-associated Kaposi Sarcoma progression under local standard-of-care therapy in Malawi and South Africa This application seeks to establish the UNC-Malawi-South Africa Cancer Consortium (UMSACC). It responds to RFA-CA-20-001 and will establish a research center to develop capacity and conduct high-impact research focused on HIV-Associated Malignancy in U.S. and Low- and Middle-Income Country. Project 2 - Kaposi Sarcoma builds on longstanding collaborations between the University of North Carolina at Chapel Hill, Lighthouse Trust / Kamuzu Central Hospital in Malawi, and Stellenbosch University / Tygerberg Hospital in South Africa. This project has participation of investigators from all three countries: the US, Malawi and South Africa. UMSACC will establish and maintain core that support mentoring, administration, pathology and analyses jointly across three projects. Kaposi sarcoma is by far the most common cancer in people living in with HIV in Sub Saharan Africa and the US standard of care, liposomal doxorubicin, is not affordable or available in the public sector. Building on recent randomized clinical trials by the AIDS malignancy Consortium and the AIDS clinical trials group, we will document the experience with paclitaxel/ cART as new first line therapy in HIV-KS and seek to develop prognostic biomarkers of the disease, such as KSHV viral load, IL6, KSHV sequence variants and KSHV transcription.